Variant 1-111238804-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004000.3(CHI3L2):c.790A>T(p.Met264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CHI3L2
NM_004000.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.219

Variant links:

Genes affected

CHI3L2 (HGNC:1933): (chitinase 3 like 2) The protein encoded by this gene is similar to bacterial chitinases but lacks chitinase activity. The encoded protein is secreted and is involved in cartilage biogenesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CHI3L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21962446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHI3L2	NM_004000.3 linkuse as main transcript	c.790A>T	p.Met264Leu	missense_variant	8/11	ENST00000369748.9	NP_003991.2
CHI3L2	NM_001025197.1 linkuse as main transcript	c.760A>T	p.Met254Leu	missense_variant	7/10		NP_001020368.1
CHI3L2	NM_001025199.2 linkuse as main transcript	c.553A>T	p.Met185Leu	missense_variant	7/10		NP_001020370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHI3L2	ENST00000369748.9 linkuse as main transcript	c.790A>T	p.Met264Leu	missense_variant	8/11	1	NM_004000.3	ENSP00000358763	P1	Q15782-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251256

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2023

The c.790A>T (p.M264L) alteration is located in exon 8 (coding exon 8) of the CHI3L2 gene. This alteration results from a A to T substitution at nucleotide position 790, causing the methionine (M) at amino acid position 264 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0094

T;.;T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.90

.;D;D;.;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.31

N;.;N;.;.

MutationTaster

Benign

0.82

N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.72

N;N;N;N;N

REVEL

Benign

0.098

Sift

Benign

0.42

T;T;T;T;T

Sift4G

Benign

0.61

T;T;T;T;T

Polyphen

0.83

P;.;P;.;.

Vest4

0.27

MutPred

0.57

Gain of catalytic residue at M264 (P = 0.0076);.;Gain of catalytic residue at M264 (P = 0.0076);.;.;

MVP

0.10

MPC

0.021

ClinPred

0.20

GERP RS

3.4

Varity_R

0.24

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over